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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی I-15: Epigenetics in Psychiatry
چکیده انگلیسی مقاله The emergence of an increasing diversity is one of the most prominent aspects of living organisms as well as neuronal cells. If one asks about the origin of the diversity of plants or animal species, the immediate response will be random mutation, consistent with the Darwinian theory of evolution. Now if one asks about the origin of the diversity of cells and tissues during the development of a single animal while the genetic make-up of all cells of that animal is the same obviously random mutations will be the most unacceptable explanation. Waddington (1939) first proposed epigenetic modulation of gene expression as the underlying mechanism of cell differentiation and the corresponding diverse structural and functional identities of those cells. However the molecular mechanism of epigenetic regulations remained unclear for decades. DNA methylation was among the earliest discovered epigenetic mechanisms mediating gene-gene and geneenvironment interactions, followed by RNA editing, histone modifications and RNA interference. As a general rule, the organic bases of DNA (genetic codes) are fixed and can transfer long-term genetic memory. However, epigenetic marks such as DNA methylation and histone acetylation are flexible and dynamic, and adapt to a variety of environmental conditions granting flexibility and adaptability to the organism. Among epigenetic mechanisms, microRNAs (miRNAs) appear to be involved in homeostatic regulation at the cellular level, preventing excess protein synthesis, and overconsumption of nucleic acids or RNA production at toxic levels. Histone acetylation and methylation are likely mechanisms for rapid response to the signals of other cells or the environment mediated by regulatory proteins, elements, hormones, and transmitters. Cellular DNA methylation status seems to be more stable and provide cell-specific epigenetic memory inherited or acquired along the entire cell life and may govern the establishment of corresponding histone codes. Similar to genetic codes, epigenetic codes are also inherited and can provide generation-specific short-term adaptive memory for the organism. However, environmental insults such as exposure to chemicals, infections and malnutrition can change epigenetic memory resulting in sporadic and, eventually, inherited developmental diseases. Based on recent reports, a large portion of genes known to be involved in psycho-pathogenesis as well as target genes of current therapeutics in psychiatry are subjects of epigenetic regulation/dysregulation. For instance, among dopaminergic and serotoninergic genes, epigenetic dysregulation of DRD2, DAT1, MB-COMT, MAOA, HTR2A and 5-HTT has been reported. Several lines of experimental evidence also provide strong support for both aberrations of DNA methylation and histone modifications in GABAergic and glutaminergic genes as well as BDNF in major psychiatric diseases. Some of these genes are actual or potential targets of known dysregulated miRNAs as well. Although these observations support the involvement of epigenetic abnormality in the pathogenesis of major mental diseases, the underlying etiology of these aberrations are yet to be uncovered and applied to preventive and therapeutic applications.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1498
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